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Dietary supplementation with resveratrol reduces plaque pathology in a transgenic model of Alzheimer’s disease

Bibliographic

Year of Publication:
2009
Contact PI Name:
Gary E. Gibson
Contact PI Affiliation:
Department of Neurology and Neurosciences, Weill Medical College of Cornell University, Burke Medical Research Institute, White Plains, New York, USA
Co-Authors:
Saravanan S. Karuppagounder, John T. Pinto, Hui Xu, Lian H. Chen, M. Flint Beal
Primary Reference (PubMED ID):
Funding Source:
Institute for the Study of Aging (ISOA)
National Institute on Aging (NIA)
Alzheimer's Drug Discovery Foundation (ADDF)
Study Goal and Principal Findings:

This study investigated effects of resveratrol on Aβ levels in AD Tg mice. Mitochondrial dysfunction and oxidative stress have been implicated in multiple neurodegenerative diseases including Alzheimer’s disease (AD), and the changes can be plausibly linked to plaque and tangle formation. Furthermore, Aβ by itself is capable of producing free radicals and ROS. The extensive data that supports an important role of oxidative stress in neurodegenerative disorders concomitantly support the beneficial effect of antioxidants as adjunctive or supportive therapy. Resveratrol possesses a wide range of biological effects that include anti-oxidative, anti-inflammatory and anti-carcinogenic properties. In vitro studies suggest that resveratrol may protect against β-amyloid induced oxidative cell damage and may promote Aβ clearance through promotion of intracellular proteosomal activity. Recent studies show that resveratrol increases longevity and delays the onset of aging in a manner similar to that of caloric restriction. In this study, mice were fed clinically feasible dosages of resveratrol for forty-five days. Neither resveratrol nor its conjugated metabolites were detectable in brain. Nevertheless, resveratrol diminished plaque formation in a region specific manner. The changes occurred without detectable activation of SIRT-1 or alterations in APP processing. However, brain glutathione declined 21% and brain cysteine increased 54%, which may be linked to the diminished plaque formation. This study supports the concept that onset of neurodegenerative disease may be delayed or mitigated with use of dietary chemo-preventive agents that protect against β-amyloid induced neuronal damage. 

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Dietary Interventions & Supplements
Therapeutic Agent:
Resveratrol
Therapeutic Target:
Multi Target

Animal Model

Model Information:
Species:
Mouse
Model Type:
APP
Strain/Genetic Background:
C57B6/SJL

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Biomarkers
Dose
Formulation
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest

Outcomes

Outcome Measured
Outcome Parameters
Histopathology
beta Amyloid Load
Dense-core/Compact Plaques
Biochemical
Cysteine
Ascorbate
Glutathione (GSH)
APP-CTFs
Sirtuins
Immunochemistry
Brain-beta Amyloid Deposits
Pharmacokinetics
Drug Concentration-Brain
Toxicology
Body Weight
Food Intake